Main manuscript
Table 1. Characteristics of the household contacts of index cholera cases in Dhaka, Bangladesh
| Category | Group | N | % | N | % |
|---|---|---|---|---|---|
| Sex | Female | 134 | 51.3 | 40 | 29.9 |
| Male | 127 | 48.7 | 37 | 29.1 | |
| Age group | 0-4 | 4 | 1.5 | 4 | 100.0 |
| 5-17 | 74 | 28.4 | 25 | 33.8 | |
| 18-49 | 164 | 62.8 | 45 | 27.4 | |
| 50-71 | 19 | 7.3 | 3 | 15.8 | |
| Self-reported history of cholera | No | 251 | 96.2 | 76 | 30.3 |
| Yes | 10 | 3.8 | 1 | 10.0 | |
| Vibriocidal titer >=320 upon enrollment | No | 226 | 86.6 | 74 | 32.7 |
| Yes | 35 | 13.4 | 3 | 8.6 | |
| Index cholera case received antibiotics | No | 181 | 69.3 | 60 | 33.1 |
| Yes | 80 | 30.7 | 17 | 21.2 | |
| Relationship to index cholera case | Child | 48 | 18.4 | 18 | 37.5 |
| Sibling | 47 | 18.0 | 15 | 31.9 | |
| Spouse | 61 | 23.4 | 15 | 24.6 | |
| Parent | 101 | 38.7 | 29 | 28.7 | |
| Diarrhea duration in index case | 0-6 days | 67 | 25.7 | 17 | 25.4 |
| 7-20 days | 92 | 35.2 | 23 | 25.0 | |
| 14-20 days | 38 | 14.6 | 12 | 31.6 | |
| 21-73 days | 64 | 24.5 | 25 | 39.1 |
Figure 1. Dynamics of functional antibody responses following V. cholerae infection
Antibody-dependent complement deposition (ADCD), cellular phagocytosis (ADCP), and neutrophil phagocytosis (ADNP) in serum from 24 index cholera cases upon enrollment (i.e., Day 2 post presumed symptom onset) and days 7 and 30 post onset. Each point represents the geometric mean of complement deposition and phagocytic scores, respectively, across three replicates. Boxplots show 50% (median), 25%, and 75% quantiles; whiskers represent approximate 95% confidence intervals for comparing medians (McGill et al. (1978)).
Figure 2. Risk of infection in household contacts of an index cholera case
Odds ratio of becoming infected among household contacts of an index cholera case for every 2-fold increase in baseline (Day 2) antibody titers, after adjusting for age and household clustering. Mean and 95% confidence interval are shown for each biomarker analyzed independently. Arrows indicate where upper confidence interval extends beyond the graph. Isotype is indicated on the left and antigen on the right for binding antibody titers. Biomarkers for which logistic model fitted values were very close to 1 are excluded.
## Dropped the following vars with logistic model fitted values very close to 1:
## IgG2OgOSP_Lx
## IgG2InOSP_Lx
## IgA2OgOSP_Lx
## IgA2InOSP_Lx
Figure 3. Biomarkers important for classifying household contacts by infection outcome
Top 15 biomarkers important in classifying household contacts of index cholera cases as infected (i.e., becoming stool positive) vs. uninfected (i.e., remaining stool negative). Biomarkers are ranked by importance scores calculated using conditional random forest classification models.
Figure 4. Predicting infection outcome among household contacts using different subsets of biomarkers
A) Cross-validated receiver operator curves (cvROC) for classifying household contacts of index cholera cases that remain uninfected vs. become infected using random forest models with different subsets of biomarkers and age. “5 biomarkers” corresponds to five of the top biomarkers selected via conditional importance, including ADCD, CtxB IgM, TcpA IgG2, Ogawa-OSP IgG1, and Sialidase IgG1. True and false positive rates calculated using leave-one-out cross-validation. B) Cross-validated area under the curve (cvAUC) corresponding to the models in A. Influence-curve based 95% confidence intervals are shown for the cvAUC estimates.
Table 2. Characteristics of North American volunteers vaccinated and then challenged with V. cholerae
| Characteristic | Category | N | No qualifying diarrhea | Mild | Moderate | Severe |
|---|---|---|---|---|---|---|
| Challenge | 11 | 34 | 29 (85.3%) | 3 (8.8%) | 1 (2.9%) | 1 (2.9%) |
| 91 | 33 | 18 (54.5%) | 11 (33.3%) | 2 (6.1%) | 2 (6.1%) | |
| Age group | 18-25 | 15 | 12 (80%) | 3 (20%) | 0 (0%) | 0 (0%) |
| 26-35 | 34 | 24 (70.6%) | 7 (20.6%) | 1 (2.9%) | 2 (5.9%) | |
| 36-45 | 18 | 11 (61.1%) | 4 (22.2%) | 2 (11.1%) | 1 (5.6%) | |
| Sex | Female | 16 | 11 (68.8%) | 3 (18.8%) | 0 (0%) | 2 (12.5%) |
| Male | 51 | 36 (70.6%) | 11 (21.6%) | 3 (5.9%) | 1 (2%) |
Figure 5. Biomarkers important for classifying vaccinees by whether or not they developed diarrhea following V. cholerae challenge
Top 15 biomarkers important in classifying vaccinees by developing either no qualifying diarrhea or mild to severe diarrhea following V. cholerae challenge. Biomarkers were selected using serum collected from participants on the day of challenge. Biomarkers are ranked by importance scores calculated using conditional random forest classification models.
Figure 6. Predicting whether or not vaccinees develop diarrhea using different subsets of biomarkers
A) Cross-validated receiver operator curves (cvROC) for classifying vaccinees that develop diarrhea vs. those that do not using random forest models with different subsets of biomarkers and age. “5 biomarkers” corresponds to five of the top biomarkers selected via conditional importance, including CT-HT IgA, CtxB IgA, CT-HT IgA2, TcpA IgA, and Sialidase IgA2. True and false positive rates calcualted using leave-one-out cross-validation. B) Cross-validated area under the curve (cvAUC) corresponding to the models in A. Influence-curve based 95% confidence intervals are shown for the cvAUC estimates.